| Structural highlights
Function
[2AAA_HUMAN] The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Required for proper chromosome segregation and for centromeric localization of SGOL1 in mitosis.[1] [ST_SV40] Promotes efficient viral genome replication by accelerating both G1 and S phase progression of the cell cycle. Inhibits host PP2A by binding to the A subunit, thereby displacing lower affinity regulatory B subunit. Inactivation of PP2A in turn results in the transactivation of cyclin A and cyclin D1 promoters. Late during the infection cycle, ST may induce dephosphorylation of host eIF4E-binding protein EIF4EBP1 leading to the inhibition of cap-dependent translation. May establish and maintain high levels of viral genomes during persistent infection in cell culture.[2] [3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The small t antigen (ST) of DNA tumor virus SV40 facilitates cellular transformation by disrupting the functions of protein phosphatase 2A (PP2A) through a poorly defined mechanism. The crystal structure of the core domain of SV40 ST bound to the scaffolding subunit of human PP2A reveals that the ST core domain has a novel zinc-binding fold and interacts with the conserved ridge of HEAT repeats 3-6, which overlaps with the binding site for the B' (also called PR61 or B56) regulatory subunit. ST has a lower binding affinity than B' for the PP2A core enzyme. Consequently, ST does not efficiently displace B' from PP2A holoenzymes in vitro. Notably, ST inhibits PP2A phosphatase activity through its N-terminal J domain. These findings suggest that ST may function mainly by inhibiting the phosphatase activity of the PP2A core enzyme, and to a lesser extent by modulating assembly of the PP2A holoenzymes.
Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40.,Chen Y, Xu Y, Bao Q, Xing Y, Li Z, Lin Z, Stock JB, Jeffrey PD, Shi Y Nat Struct Mol Biol. 2007 Jun;14(6):527-34. Epub 2007 May 27. PMID:17529992[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, Yu H. PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation. Dev Cell. 2006 May;10(5):575-85. Epub 2006 Mar 30. PMID:16580887 doi:10.1016/j.devcel.2006.03.010
- ↑ Skoczylas C, Henglein B, Rundell K. PP2A-dependent transactivation of the cyclin A promoter by SV40 ST is mediated by a cell cycle-regulated E2F site. Virology. 2005 Feb 20;332(2):596-601. PMID:15680424 doi:10.1016/j.virol.2004.12.017
- ↑ Yu Y, Kudchodkar SB, Alwine JC. Effects of simian virus 40 large and small tumor antigens on mammalian target of rapamycin signaling: small tumor antigen mediates hypophosphorylation of eIF4E-binding protein 1 late in infection. J Virol. 2005 Jun;79(11):6882-9. PMID:15890927 doi:http://dx.doi.org/10.1128/JVI.79.11.6882-6889.2005
- ↑ Fahrbach KM, Katzman RB, Rundell K. Role of SV40 ST antigen in the persistent infection of mesothelial cells. Virology. 2008 Jan 20;370(2):255-63. Epub 2007 Oct 23. PMID:17936323 doi:http://dx.doi.org/S0042-6822(07)00593-4
- ↑ Porras A, Bennett J, Howe A, Tokos K, Bouck N, Henglein B, Sathyamangalam S, Thimmapaya B, Rundell K. A novel simian virus 40 early-region domain mediates transactivation of the cyclin A promoter by small-t antigen and is required for transformation in small-t antigen-dependent assays. J Virol. 1996 Oct;70(10):6902-8. PMID:8794333
- ↑ Watanabe G, Howe A, Lee RJ, Albanese C, Shu IW, Karnezis AN, Zon L, Kyriakis J, Rundell K, Pestell RG. Induction of cyclin D1 by simian virus 40 small tumor antigen. Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):12861-6. PMID:8917510
- ↑ Chen Y, Xu Y, Bao Q, Xing Y, Li Z, Lin Z, Stock JB, Jeffrey PD, Shi Y. Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40. Nat Struct Mol Biol. 2007 Jun;14(6):527-34. Epub 2007 May 27. PMID:17529992 doi:10.1038/nsmb1254
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